Summary of treatment results of recent clinical trials for children and adolescents newly diagnosed with T-cell lymphoblastic lymphoma
| Trial (study y) . | Study population . | T-LL patients (total number of accrued patients) . | Backbone . | %EFS; %OS . | Induction steroid (daily dose) . | CNS radiation . | Toxicity . |
|---|---|---|---|---|---|---|---|
| LMT81 (1981-1989)18 | I-IV | 84 | Modified LSA2-L2 | 75%; 76% | Pred 60 mg/m2 | Added 24 Gy for CNS + pts in 1985 to be given during maintenance | No added toxicity from HDMTX compared with control |
| CCG502 (1983-1990)1 | I-IV | 143 | Modified LSA2-L2 | 74% (P = .17) | Pred 60 mg/m2 | CNS + pts, given 24 Gy during maintenance | Increased gr 3/4 neutropenia and thrombocytopenia with LSA2L2 |
| 138 | ADCOMP | 64% | Pred 60 mg/m2 | ||||
| POG 8704 (1987-1992)19 | III/IV | 83 | w/l-asparaginase | 78% ± 5% (P = .048) | Pred 40 mg/m2 | CNS + pts, given 24 Gy during maintenance | Increased allergic reactions on the asparaginase arm (24% vs 10%) |
| 84 | w/o l-asparaginase | 64% ± 6% | |||||
| NHL-BFM90 (1990-1995)2 | I-IV (>95% III/IV) | 105 | ALL-BFM | 90% (CI 0.82-1.0) | Pred 60 mg/m2 | All pts given 12 Gy before maintenance | No TR deaths |
| NHL-BFM95 (1995-2001)20 | CNS negative III/IV T and B LL | 126 (156) | ALL-BFM | 78%; 83% | Pred 40 mg/m2 | Given to CNS + pts only after reintensification and these patients were excluded from analysis | Similar to previous trials |
| EORTC58881 (1989-1998)21 | I-IV | 119 | ALL-BFM | 78% ± 4% | Pred 60 mg/m2 | No prophylactic CRT given | Similar to previous trials |
| LNH92 (1992-1997)22 | I-IV | 47 (55) | Modified LSA2-L2 | 69%; 72% | Pred 60 mg/m2 | 18Gy for CNS + pts in maintenance | No TR deaths, increased Grade 3-4 toxicity with more inteinsive maintenance |
| St. Jude NHL 13 (1992-2002)23 | III/IV | 33 (41) | T-ALL | 83%; 90% | Pred 40 mg/m2 | None | Not reported |
| POG 9404 (1996-2001)24 | Stage III/IV | 137 (436) | Modified DFCI ALL | (P = .38) | Pred 40 mg/m2 | All patients 18 Gy during consolidation | 3 patients with T-LL with deaths as first event, but does not specify from what causes. Only statistically significant difference in toxicity was mucositis HDMTX vs not 17.8% vs 8% (P = .003) |
| 66 | w/HDMTX | 81.7%; 84.5% | |||||
| 71 | w/o HDMTX | 87.8%; 89.2% | |||||
| T-ALL | 299 (436) | Modified DFCI ALL | Pred 40 mg/m2 | All patients 18 Gy during consolidation | |||
| 148 | w/HDMTX | 79.5%; 84.3% | |||||
| 151 | w/o HDMTX | 67.5%; 74.7% | |||||
| SFOP LMT96 (1997-2003)25 | Stage I-IV | 79 | Modified BFM | 85%; 89% | Pred 60 mg/m2 | CNS+ received 18 Gy before maintenance | No TR deaths. 58% had grade 3-4 neutropenia by end induction |
| EORTC 58951 (1999-2008)21,26 | 74 (1947) | Modified BFM 90 | 85% | Total | Increased mortality in Dex group while in CR | ||
| 37 | 81% ± 6% | Dex (6 mg/m2) | None | ||||
| 37 | 89% ± 5% | Pred (60 mg/m2) | |||||
| T-ALL | 296 (1947) | Modified BFM 90 | 81.3%; 88.1% | Total | |||
| 71.3%; 74.2% | Dex (6 mg/m2) | ||||||
| 82.1%; 89% | Pred (60 mg/m2) | ||||||
| A5971 (2000-2005)17 | Stage I/II | 8 (56) | CCG-BFM | 90%; 96% | Pred (60 mg/m2) | None | Grade 3-4 toxicities in <10% during induction except for ALT elevation |
| A5971 (2000-2005)27 | Stage III/IV | 266 T&B-LL | NHL-BFM95 (with HDMTX) | (P = .62 comparing intensified vs not and 0.97 compating HDMTX vs not) | CNS+ received 18 Gy during maintenance | % patients with grade 3-4 toxicity by arm | |
| No intensification | 84%; 85% | Pred | 22% | ||||
| Intensification | 80%; 85% | 91% | |||||
| CCG mod BFM (no HDMTX) | Pred | ||||||
| No intensification | 81%; 84% | 22% | |||||
| Intensification | 80%; 88% | 92% | |||||
| EURO LB-02 (2004-2008)28 | Stage I-IV | 233 (319) | NHL/ALL-BFM 90 | 81% ± 2% | CNS + pts received RT after reintensification | Higher incidence of grade III/IV toxicities (includes infectious complications in induction) in dexamethasone group, CNS relapses higher in prednisone vs dexamethasone (4% vs 0%; P = .03) but similar overall relapses | |
| 98 | 84% ± 4% | Dex (10 mg/m2) | |||||
| 88 | 84% ± 4% | Pred (60 mg/m2) | |||||
| AALL0434 (2010-2014)29,30 | II-IV, >1% MMD in BM | 299 (1861) | COG-BFM | 84.7%; 89% (P = .55) | Pred 60 mg/m2 | No prophlylactic CRT given | Toxicity similar with nelarabine vs not except for peripheral sensory neuropathy (26 Nel vs 13 not P = .005) |
| w/nelarabine | 85.0% ± 4.9% | (CNS 3 excluded) | |||||
| w/o nelarabine | 85.1% ± 4.8% | ||||||
| T-ALL | 1562 (1861) | COG-BFM | 83.7%; 89.5% | Pred 60 mg/m2 | all patients except those with LR disease received 12 Gy of CRT | ||
| w/nelarabine | 88.2%; 90.3% | ||||||
| w/o nelarabine | 82.1%; 87.9% | ||||||
| AALL1231 (2014-2017)31 | II-IV | 209 (824) | COG-BFM | (P = .41 for EFS, 0.009 for OS) | Dex 6 mg/m2 | CRT given to CNS 3 patients only | Overall grade 3-4 toxicity rates were similar between bortez and not bortez |
| w/bortezomib | 86.4%; 89.5% | ||||||
| w/o bortezomib | 76.5%; 78.3% | ||||||
| T-ALL | 615 (824) | COG-BFM | Dex 6 mg/m2 | CRT given to all VHR pts and CNS3 IR pts | |||
| w/bortezomib | 83.8%; 88.3% | ||||||
| w/o bortezomib | 80.1%; 85.7% | ||||||
| Trial (study y) . | Study population . | T-LL patients (total number of accrued patients) . | Backbone . | %EFS; %OS . | Induction steroid (daily dose) . | CNS radiation . | Toxicity . |
|---|---|---|---|---|---|---|---|
| LMT81 (1981-1989)18 | I-IV | 84 | Modified LSA2-L2 | 75%; 76% | Pred 60 mg/m2 | Added 24 Gy for CNS + pts in 1985 to be given during maintenance | No added toxicity from HDMTX compared with control |
| CCG502 (1983-1990)1 | I-IV | 143 | Modified LSA2-L2 | 74% (P = .17) | Pred 60 mg/m2 | CNS + pts, given 24 Gy during maintenance | Increased gr 3/4 neutropenia and thrombocytopenia with LSA2L2 |
| 138 | ADCOMP | 64% | Pred 60 mg/m2 | ||||
| POG 8704 (1987-1992)19 | III/IV | 83 | w/l-asparaginase | 78% ± 5% (P = .048) | Pred 40 mg/m2 | CNS + pts, given 24 Gy during maintenance | Increased allergic reactions on the asparaginase arm (24% vs 10%) |
| 84 | w/o l-asparaginase | 64% ± 6% | |||||
| NHL-BFM90 (1990-1995)2 | I-IV (>95% III/IV) | 105 | ALL-BFM | 90% (CI 0.82-1.0) | Pred 60 mg/m2 | All pts given 12 Gy before maintenance | No TR deaths |
| NHL-BFM95 (1995-2001)20 | CNS negative III/IV T and B LL | 126 (156) | ALL-BFM | 78%; 83% | Pred 40 mg/m2 | Given to CNS + pts only after reintensification and these patients were excluded from analysis | Similar to previous trials |
| EORTC58881 (1989-1998)21 | I-IV | 119 | ALL-BFM | 78% ± 4% | Pred 60 mg/m2 | No prophylactic CRT given | Similar to previous trials |
| LNH92 (1992-1997)22 | I-IV | 47 (55) | Modified LSA2-L2 | 69%; 72% | Pred 60 mg/m2 | 18Gy for CNS + pts in maintenance | No TR deaths, increased Grade 3-4 toxicity with more inteinsive maintenance |
| St. Jude NHL 13 (1992-2002)23 | III/IV | 33 (41) | T-ALL | 83%; 90% | Pred 40 mg/m2 | None | Not reported |
| POG 9404 (1996-2001)24 | Stage III/IV | 137 (436) | Modified DFCI ALL | (P = .38) | Pred 40 mg/m2 | All patients 18 Gy during consolidation | 3 patients with T-LL with deaths as first event, but does not specify from what causes. Only statistically significant difference in toxicity was mucositis HDMTX vs not 17.8% vs 8% (P = .003) |
| 66 | w/HDMTX | 81.7%; 84.5% | |||||
| 71 | w/o HDMTX | 87.8%; 89.2% | |||||
| T-ALL | 299 (436) | Modified DFCI ALL | Pred 40 mg/m2 | All patients 18 Gy during consolidation | |||
| 148 | w/HDMTX | 79.5%; 84.3% | |||||
| 151 | w/o HDMTX | 67.5%; 74.7% | |||||
| SFOP LMT96 (1997-2003)25 | Stage I-IV | 79 | Modified BFM | 85%; 89% | Pred 60 mg/m2 | CNS+ received 18 Gy before maintenance | No TR deaths. 58% had grade 3-4 neutropenia by end induction |
| EORTC 58951 (1999-2008)21,26 | 74 (1947) | Modified BFM 90 | 85% | Total | Increased mortality in Dex group while in CR | ||
| 37 | 81% ± 6% | Dex (6 mg/m2) | None | ||||
| 37 | 89% ± 5% | Pred (60 mg/m2) | |||||
| T-ALL | 296 (1947) | Modified BFM 90 | 81.3%; 88.1% | Total | |||
| 71.3%; 74.2% | Dex (6 mg/m2) | ||||||
| 82.1%; 89% | Pred (60 mg/m2) | ||||||
| A5971 (2000-2005)17 | Stage I/II | 8 (56) | CCG-BFM | 90%; 96% | Pred (60 mg/m2) | None | Grade 3-4 toxicities in <10% during induction except for ALT elevation |
| A5971 (2000-2005)27 | Stage III/IV | 266 T&B-LL | NHL-BFM95 (with HDMTX) | (P = .62 comparing intensified vs not and 0.97 compating HDMTX vs not) | CNS+ received 18 Gy during maintenance | % patients with grade 3-4 toxicity by arm | |
| No intensification | 84%; 85% | Pred | 22% | ||||
| Intensification | 80%; 85% | 91% | |||||
| CCG mod BFM (no HDMTX) | Pred | ||||||
| No intensification | 81%; 84% | 22% | |||||
| Intensification | 80%; 88% | 92% | |||||
| EURO LB-02 (2004-2008)28 | Stage I-IV | 233 (319) | NHL/ALL-BFM 90 | 81% ± 2% | CNS + pts received RT after reintensification | Higher incidence of grade III/IV toxicities (includes infectious complications in induction) in dexamethasone group, CNS relapses higher in prednisone vs dexamethasone (4% vs 0%; P = .03) but similar overall relapses | |
| 98 | 84% ± 4% | Dex (10 mg/m2) | |||||
| 88 | 84% ± 4% | Pred (60 mg/m2) | |||||
| AALL0434 (2010-2014)29,30 | II-IV, >1% MMD in BM | 299 (1861) | COG-BFM | 84.7%; 89% (P = .55) | Pred 60 mg/m2 | No prophlylactic CRT given | Toxicity similar with nelarabine vs not except for peripheral sensory neuropathy (26 Nel vs 13 not P = .005) |
| w/nelarabine | 85.0% ± 4.9% | (CNS 3 excluded) | |||||
| w/o nelarabine | 85.1% ± 4.8% | ||||||
| T-ALL | 1562 (1861) | COG-BFM | 83.7%; 89.5% | Pred 60 mg/m2 | all patients except those with LR disease received 12 Gy of CRT | ||
| w/nelarabine | 88.2%; 90.3% | ||||||
| w/o nelarabine | 82.1%; 87.9% | ||||||
| AALL1231 (2014-2017)31 | II-IV | 209 (824) | COG-BFM | (P = .41 for EFS, 0.009 for OS) | Dex 6 mg/m2 | CRT given to CNS 3 patients only | Overall grade 3-4 toxicity rates were similar between bortez and not bortez |
| w/bortezomib | 86.4%; 89.5% | ||||||
| w/o bortezomib | 76.5%; 78.3% | ||||||
| T-ALL | 615 (824) | COG-BFM | Dex 6 mg/m2 | CRT given to all VHR pts and CNS3 IR pts | |||
| w/bortezomib | 83.8%; 88.3% | ||||||
| w/o bortezomib | 80.1%; 85.7% | ||||||
ALT, alanine transaminase; Dex, dexamethasone; IR, intermediate risk; OS, overall survival; Pred, prednisone; RT, radiation therapy; TR, treatment related; VHR, very high risk; w/, with; w/o, without.